Assessing the accuracy of pleural puncture sites in patients with pleural effusion as determined by clinical examination versus ultrasound-A single-centre prospective study.

INTRODUCTION: This study aimed to ascertain the accuracy of clinical examination for the determination of pleural puncture sites as compared to the use of ultrasonography in patients with pleural effusion. MATERIAL AND METHODS: A single-centre, prospective, observational study was carried out amongst 115 patients with pleural effusion in a tertiary care hospital in western India. Patients were subjected to clinical assessment for determination of pleural puncture sites and the same were confirmed with ultrasonography. All physicians were blinded to the marking of the previous physician to prevent any influence on their assessment. RESULTS: The study had 345 physician observations. The overall accuracy of the clinical examination was 94.8%. Multivariate logistic regression of the factors responsible for the accuracy of clinical examination demonstrated a significant role of higher body mass index (BMI) (OR-1.19) and lower zone pleural effusions (OR-4.99) when adjusted for age, gender, side of effusion, and experience of examining doctors. When the effusions were classified according to their location, lower zone pleural effusions and loculated pleural effusions had an error rate of 15.9% and 8.33%, respectively. CONCLUSION: An ultrasound is the standard of care to assess all pleural effusions and guide the best point for aspiration.

Retrospective Analysis of Spectrum of Infections and Antibiotic Resistance Pattern in Chronic Kidney Disease Patients on Maintenance Hemodialysis in a Tertiary Care Centre in North India.

Introduction: Hemodialysis patients are at risk of infections. This study examines the spectrum of infections and antibiotic resistance patterns. Methods: We retrospectively reviewed the records of 586 hemodialysis patients from May 2018 to April 2020 in a tertiary care hospital in North India. Results: The study identified 99 episodes of confirmed infections. Urinary tract infections were the most common type of infections (55.5%), followed by catheter-related bloodstream infections (CRBSI) (definitive 21.2%). Other infections were pneumonia (8.1%), tuberculosis (6.1%), skin and soft tissue infection (4.0%), dengue fever (3.03%), and empyema thoracis (1.0%). Overall, Escherichia coli (33.3%) was the most common organism isolated. The most frequent uropathogens recovered were Escherichia coli (54%). In confirmed CRBSI, P. aeruginosa (23.8%) and MSSA (23.8%) were the most common pathogen isolated. K. pneumonia (37.5%) was the most common pathogen in pneumonia. Uropathogens showed the highest resistance to fluoroquinolones (93.3%-100%). Pathogens isolated in CRBSI showed maximum resistance to ciprofloxacin (100%). In pneumonia, the highest resistance was seen to third-generation cephalosporins (75%-100%). Conclusion: Though the bacterial spectrum remains the same over time, antibiotic resistance is changing in uropathogens. There is a trend of predominance of Gram-negative bacterial infections in CRBSI. Tuberculosis incidence rate was much higher than the general population. There is a need for nationwide and worldwide continuous surveillance.

Metformin mediates MicroRNA-21 regulated circulating matrix metalloproteinase-9 in diabetic nephropathy: an in-silico and clinical study.

Metformin is commonly used as an oral hypoglycaemic agent in type 2 diabetes mellitus (T2DM). MicroRNA-21 is widely studied in diabetic and diabetic nephropathy (DN) patients. Matrix metalloproteinase-9 (MMP9) is involved in extracellular matrix degradation and tissue repair processes. However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients. The study subjects were divided into three groups (Healthy controls = 36, T2DM = 38, DN = 35). Anthropometric measurements were taken and biochemical tests were carried out on fasting blood samples. Reverse transcriptase PCR was employed for whole blood gene expression analysis of hsa-miR-21-5p and MMP9. Bioinformatics analyses including drug-gene interaction, protein-protein interaction, functional enrichment analyses and co-expression networks were performed. In the present study, MMP9 and hsa-miR-21-5p levels were downregulated and upregulated respectively in T2DM and DN patients when compared with healthy controls. However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed. In-silico analysis revealed the target genes involved in the miR-21 and MMP9 interaction network. Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.

A clinical and in-silico study of microRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors. METHODS: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR. RESULTS: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients. CONCLUSIONS: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.

Renal Allograft Malakoplakia Presenting as a Pseudotumoral Lesion.

Malakoplakia is an uncommon inflammatory disease that can involve many organ systems but is often encountered in the urogenital tract. Kidney allograft malakoplakia is even rarer and can have a diffuse parenchymal or a pseudotumoral presentation. We describe a case of grafi malakoplakia in an adult female, who presented with dull aching pain in the right loin, fever, and vomiting. Ultrasonography of the kidney graft showed a heterogeneous lesion (2.6 cm × 2.9 cm), raising suspicion of primary or metastatic renal tumors. The diagnosis was established after a histopathological examination of the kidney biopsy. This pseudotumoral presentation of malakoplakia can mimic renal cell carcinoma, lymphoma, fungal infections, or tuberculosis. It is essential to perform a biopsy for establishing the diagnosis.

The Differentially Expressed Genes Responsible for the Development of T Helper 9 Cells From T Helper 2 Cells in Various Disease States: Immuno-Interactomics Study.

BACKGROUND: T helper (Th) 9 cells are a novel subset of Th cells that develop independently from Th2 cells and are characterized by the secretion of interleukin (IL)-9. Studies have suggested the involvement of Th9 cells in variable diseases such as allergic and pulmonary diseases (eg, asthma, chronic obstructive airway disease, chronic rhinosinusitis, nasal polyps, and pulmonary hypoplasia), metabolic diseases (eg, acute leukemia, myelocytic leukemia, breast cancer, lung cancer, melanoma, pancreatic cancer), neuropsychiatric disorders (eg, Alzheimer disease), autoimmune diseases (eg, Graves disease, Crohn disease, colitis, psoriasis, systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atopic dermatitis, eczema), and infectious diseases (eg, tuberculosis, hepatitis). However, there is a dearth of information on its involvement in other metabolic, neuropsychiatric, and infectious diseases. OBJECTIVE: This study aims to identify significant differentially altered genes in the conversion of Th2 to Th9 cells, and their regulating microRNAs (miRs) from publicly available Gene Expression Omnibus data sets of the mouse model using in silico analysis to unravel various pathogenic pathways involved in disease processes. METHODS: Using differentially expressed genes (DEGs) identified from 2 publicly available data sets (GSE99166 and GSE123501) we performed functional enrichment and network analyses to identify pathways, protein-protein interactions, miR-messenger RNA associations, and disease-gene associations related to significant differentially altered genes implicated in the conversion of Th2 to Th9 cells. RESULTS: We extracted 260 common downregulated, 236 common upregulated, and 634 common DEGs from the expression profiles of data sets GSE99166 and GSE123501. Codifferentially expressed ILs, cytokines, receptors, and transcription factors (TFs) were enriched in 7 crucial Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology. We constructed the protein-protein interaction network and predicted the top regulatory miRs involved in the Th2 to Th9 differentiation pathways. We also identified various metabolic, allergic and pulmonary, neuropsychiatric, autoimmune, and infectious diseases as well as carcinomas where the differentiation of Th2 to Th9 may play a crucial role. CONCLUSIONS: This study identified hitherto unexplored possible associations between Th9 and disease states. Some important ILs, including CCL1 (chemokine [C-C motif] ligand 1), CCL20 (chemokine [C-C motif] ligand 20), IL-13, IL-4, IL-12A, and IL-9; receptors, including IL-12RB1, IL-4RA (interleukin 9 receptor alpha), CD53 (cluster of differentiation 53), CD6 (cluster of differentiation 6), CD5 (cluster of differentiation 5), CD83 (cluster of differentiation 83), CD197 (cluster of differentiation 197), IL-1RL1 (interleukin 1 receptor-like 1), CD101 (cluster of differentiation 101), CD96 (cluster of differentiation 96), CD72 (cluster of differentiation 72), CD7 (cluster of differentiation 7), CD152 (cytotoxic T lymphocyte-associated protein 4), CD38 (cluster of differentiation 38), CX3CR1 (chemokine [C-X3-C motif] receptor 1), CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha), CTLA28, and CD196 (cluster of differentiation 196); and TFs, including FOXP3 (forkhead box P3), IRF8 (interferon regulatory factor 8), FOXP2 (forkhead box P2), RORA (RAR-related orphan receptor alpha), AHR (aryl-hydrocarbon receptor), MAF (avian musculoaponeurotic fibrosarcoma oncogene homolog), SMAD6 (SMAD family member 6), JUN (Jun proto-oncogene), JAK2 (Janus kinase 2), EP300 (E1A binding protein p300), ATF6 (activating transcription factor 6), BTAF1 (B-TFIID TATA-box binding protein associated factor 1), BAFT (basic leucine zipper transcription factor), NOTCH1 (neurogenic locus notch homolog protein 1), GATA3 (GATA binding protein 3), SATB1 (special AT-rich sequence binding protein 1), BMP7 (bone morphogenetic protein 7), and PPARG (peroxisome proliferator-activated receptor gamma, were able to identify significant differentially altered genes in the conversion of Th2 to Th9 cells. We identified some common miRs that could target the DEGs. The scarcity of studies on the role of Th9 in metabolic diseases highlights the lacunae in this field. Our study provides the rationale for exploring the role of Th9 in various metabolic disorders such as diabetes mellitus, diabetic nephropathy, hypertensive disease, ischemic stroke, steatohepatitis, liver fibrosis, obesity, adenocarcinoma, glioblastoma and glioma, malignant neoplasm of stomach, melanoma, neuroblastoma, osteosarcoma, pancreatic carcinoma, prostate carcinoma, and stomach carcinoma.

Relationship between biochemical parameters of mineral bone disease and static bone histomorphometry in chronic kidney disease patients on hemodialysis: An Indian cross-section study.

AIM: We estimated the relationship between routine biochemical laboratory parameters with static bone histomorphometric parameters and their high and low bone turnover capacity predictability in hemodialysis patients. METHOD: It was a single-center cross-sectional study, included 28 hemodialysis patients. The routine biochemical parameters measured including calcium, phosphorous, alkaline phosphatase, intact PTH, and 25-hydroxycholecalciferol. The histomorphometric parameters assessed were osteoblasts perimeter, osteoclast perimeter, eroded perimeter, osteoid perimeter, bone fibrosis and bone volume. RESULT: Total 28 hemodialysis patients underwent bone biopsy. Seventy percent were male, with a mean age was 33.07±10.42 yrs; serum alkaline phosphatase was 219.10±311.3IU/ml; vitamin D was 18.18±9.56ng/ml, and intact PTH was 650.7±466.0pg/ml. Intact PTH had a significant positive association with osteoblast, osteoclast, eroded surface, and osteoid perimeter. Serum alkaline phosphatase had a significant relationship with bone fibrosis (r=0.525, p-value=0.004). Intact PTH was significantly higher in females than males (1078.75±533.04 vs. 479.6±309.83; p-value=0.004). The osteoid surface was significantly high in females compared to males (p=0.038). Age had a significant impact on osteoblast and eroded surface (p=0.008 and p=0.031, respectively). Intact PTH is a reliable biomarkers for bone turnover compare to ALP (p<0.001 and p=0.554, respectively). CONCLUSION: Intact PTH strongly associated with bone formation, bone resorption parameters. Gender and age had significant impact on static histomorphometric parameters in our study.

Dietary Determinants of Renal Calculi: A Case-Control Study From a Tertiary Care Hospital of Western Rajasthan.

Introduction Nephrolithiasis affects all countries of the world with an approximate global lifetime prevalence of 15-20%. In India, 12% of the total population is anticipated to have renal stone disease. This study was aimed at providing a relationship between various dietary factors in the formation of renal stones. Methods A case-control study was conducted among 207 patients (106 cases and 101 controls) attending the outpatient and inpatient departments of a tertiary care hospital in Jodhpur, Rajasthan. All the participants with confirmed renal stones by means of ultrasound and radiographic evaluation, aged 15-65 years were included as cases and were matched on age and gender with controls. Pearson chi-square test followed by binary logistic regression was used to assess significant associations. Results Out of all participants, 71.0% were males and 65.7% were from the age group 41-65 years. The study showed a statistically significant association between renal stones and high salt intake, reduced water intake, less consumption of milk and milk products, daily intake of tea, consumption of oxalate-rich foods and consumption of junk foods. Conclusion Dietary factors play an important role in the risk of the development of renal stones. Simple dietary modifications may significantly reduce the chances of the development of nephrolithiasis, especially in the vulnerable population.

Does Quality Certification Work? An Assessment of Manyata, a Childbirth Quality Program in India's Private Sector.

BACKGROUND: In India, more than 60% of hospital beds are in private facilities, yet several studies have observed suboptimal quality of care in private facilities. We aimed to understand the role of Manyata, a quality improvement initiative in private facilities focused on mentorship and clinical standards, to improve the knowledge and skills of health care providers, their adherence to key childbirth-related clinical practices, and health outcomes for women and newborns. METHODS: We conducted a secondary analysis of Manyata program data collected from 466 private facilities across 3 states (Jharkhand, Maharashtra, and Uttar Pradesh) in India from October 2016 to February 2019. We calculated means and 95% confidence intervals for knowledge and skills assessment, adherence to facility standards was analyzed by calculating the proportion of facilities passing a given quality standard at baseline and endline, and changes in pregnancy outcomes were assessed with autoregression modeling. RESULTS: From assessments conducted before and after training among providers in Manyata, we observed a significant increase in average knowledge score (6.3 vs. 13.2 of 20) and skill score (8.0 vs. 34.3 of 40). Overall, a significant increase occurred in adherence to clinical standards between baseline and endline assessments (29% vs. 93%). The standards with the greatest improvements were identification and management of eclampsia/preeclampsia, postpartum hemorrhage, and neonatal resuscitation. There were no significant changes over time in absolute rate of reported complications; however, referral rates from private facilities for preeclampsia and newborn sepsis identification and management declined. CONCLUSION: Our analysis indicates private facilities' adherence to quality standards and nurses' childbirth knowledge and practical skills increased during Manyata. Additional efforts are needed to ensure high-quality care during cesarean deliveries at private facilities. Future studies with rigorous design are required to evaluate the impact of this quality improvement initiative in improving pregnancy outcomes.

Current Status and Future of Artificial Kidney in Humans.

The number of patients needing renal replacement therapy (RRT) is increasing rapidly with an increase in lifestyle diseases such as diabetes, hypertension, and metabolic syndrome. Kidney transplantation, whenever feasible, is the most preferred mode of RRT. However, there is a growing shortage of donor kidneys for transplantation. While dialysis is partially able to perform the filtration and excretion function of the kidneys, it is still not able to perform the other renal tubular and endocrine functions of a normal kidney and has quality-of-life issues with significant long-term morbidity. The need of the hour is to develop an ideal artificial kidney that would be wearable or implantable and would be able to perform the complete excretory, filtration, tubular, endocrine, and metabolic functions of the kidney while preserving the quality of life and minimizing complications. In this review, we discuss the characteristics of an ideal artificial kidney, the challenges of developing such a device, a brief description of the past and current work on this topic, and what the artificial kidney of the future should look like.

A Rare Fatal Cause of Acute Areflexic Quadriparesis in the Tropics.

BACKGROUND: Crimean-Congo hemorrhagic fever is a sporadic zoonotic viral illness recently becoming endemic in regions in the western parts of India. It usually presents as a viral hemorrhagic fever with severe liver and kidney failure. CASE REPORT: An 18-year-old male from the western part of Rajasthan presented with rapidly progressing areflexic weakness of limbs a week after brief fever. He deteriorated rapidly with drowsiness, fulminant liver failure, and acute kidney injury with high creatine kinase. He also developed thrombocytopenia and hemorrhage from various sites. Workup for viral hemorrhagic fever revealed IgM positivity for Crimean-Congo hemorrhagic fever. The patient kept worsening and died of multiorgan failure and diffuse alveolar bleeding after 14 days. CONCLUSIONS: This report highlights the need to expand the differential diagnoses in the commonly encountered presentation of acute quadriparesis to include the possibility of tick-borne diseases like Crimean-Congo hemorrhagic fever in the setting of bleeding diathesis and acute hepatorenal syndrome.

Focal segmental glomerulosclerosis in a patient with prefibrotic primary myelofibrosis.

We report a case of 56-year-old man presented to us with chief complaints of frothy urine and leg swelling. A urinalysis revealed nephrotic-range proteinuria. Haematological investigations revealed thrombocytosis, leucocytosis and peripheral blood smear showed a leucoerythroblastic picture. JAK 2 mutation was positive. To confirm the diagnosis of myeloproliferative neoplasm, bone marrow biopsy was done, which was suggestive of primary myelofibrosis. The patient underwent kidney biopsy due to rapidly declining renal function and persistent proteinuria, which was suggestive of focal segmental glomerulosclerosis. Early glomerulopathy is rare in myeloproliferative neoplasm, and aggressive follow-up is required to prevent progression of kidney disease.

Daily plasma exchange in severe Guillain-Barré syndrome helps in early weaning from ventilator: A lesson from a case.

Intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE) are well-known therapeutic modalities in Guillain-Barré syndrome (GBS). In developing countries like India, where plasma-derived products (IVIG) are not easily available, and affordable TPE is preferred. Here, we reported a case of severe GBS, who was treated with daily plasma exchange (PLEX) rather than recommended alternate day schedule. A 16-year-old male adolescent of severe GBS, i.e., on mechanical ventilator was treated with the plasmapheresis regimen consisted of removal of 1.3 plasma volumes in each cycle for total of five cycles, on daily basis. The patient's condition started improving after three cycles of TPE with power in the upper limbs 4/5 and lower limbs 3/5 and completely weaned off from ventilator after the 4th TPE, i.e. the 4th day of admission. This case emphasizes the need of daily PLEX regimen particularly in severe GBS patients because early weaning from ventilator reduces the ventilator-associated complications, hospital stay as wells as less morbidity, and mortality in severe GBS.

Metabolite characterisation in peritoneal dialysis effluent using high-resolution (1) H and (1) H-(13) C NMR spectroscopy.

Metabolite analysis of peritoneal dialysis (PD) effluent may provide information regarding onset and progression of complications associated with prolonged PD therapy. In this context, the nuclear magnetic resonance detectable small metabolites of PD effluent samples were characterised using high-resolution (1) H and (1) H-(13) C NMR spectroscopy. The various spectra were recorded (at 800 MHz proton frequency) on PD effluent samples obtained after 4-h (intraperitoneal) dwell time from patients with end-stage renal failure and continuing normally on PD therapy. In spite of devastating spectral feature of PD effluent due to the presence of intense resonances from glucose and lactate, we were able to identify 53 small endogenous metabolites (including many complex coupled spin systems) and more than 90% of the total CH cross peaks of (1) H-(13) C heteronuclear single-quantum correlation spectrum specific to various metabolites of PD effluent. We foresee that the characteristic fingerprints of various metabolites of control PD effluent samples will be used to identify and distinguish metabolic differences from PD-related complications.